1. Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets
- Author
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Lei Li, Peter Halfmann, Maria Lucia Madariaga, Siriruk Changrob, Nicholas Asby, Florian Krammer, Kumaran Shanmugarajah, Maud O. Jansen, Isabelle Stewart, Ya Nan Dai, Andrzej Joachimiak, Steven A. Erickson, Haley L. Dugan, Yoshihiro Kawaoka, Jenna J. Guthmiller, Henry A. Utset, Paige D. Hall, Jiaolong Wang, Emma S. Winkler, Christopher T. Stamper, Mari Cobb, Olivia Stovicek, Daved H. Fremont, Michael S. Diamond, Fatima Amanat, Christopher A. Nelson, Patrick C. Wilson, Jun Huang, Robert Jedrzejczak, Dustin G. Shaw, Nai Ying Zheng, and Min Huang
- Subjects
Male ,0301 basic medicine ,medicine.drug_class ,Immunology ,Immunodominance ,Cross Reactions ,Antibodies, Viral ,Monoclonal antibody ,Article ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Neutralization Tests ,medicine ,Humans ,Immunology and Allergy ,Memory B cell ,B cell ,B-Lymphocytes ,biology ,Immunodominant Epitopes ,SARS-CoV-2 ,Gene Expression Profiling ,COVID-19 ,Computational Biology ,High-Throughput Nucleotide Sequencing ,virus diseases ,Antibodies, Neutralizing ,Virology ,Nucleoprotein ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Epitope mapping ,030220 oncology & carcinogenesis ,Antibody Formation ,Host-Pathogen Interactions ,Spike Glycoprotein, Coronavirus ,biology.protein ,Female ,Single-Cell Analysis ,Antibody ,Transcriptome ,Immunologic Memory ,Epitope Mapping - Abstract
Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we utilized single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post-symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs., Graphical Abstract, Dugan et al. utilize a multi-antigen bait sorting and single cell sequencing approach to profile B cell immunodominance upon SARS-CoV-2 infection, revealing a dynamic response that evolves toward internal virus proteins over time. Antibodies to internal proteins were non-protective in vivo, suggesting vaccination may generate superior anti-spike immunological memory.
- Published
- 2021